GOOD HEALTH MAGAZINE : Medicine : ON TRIAL : ‘WHAT YOU HAVE IS AN ADVANTAGE OF GETTING THESE DRUGS BEFORE THEY’RE LICENSED. THAT COULD TAKE FIVE, MAYBE 10 YEARS. YOU COULD BE DEAD IN THE MEANTIME’

When Carol Schieber learned in October, 1987, that cancer had spread from her breast to her lungs and liver, she discussed her alternatives with a specialist, then opted against standard therapy in favor of experimental treatment.

The choice was quite simple, Schieber recalls: It seemed the experimental treatment would be better tailored to her case. If the drugs worked and were eventually approved for widespread use, she would have got in on a good thing early.

“What you have is an advantage of getting these drugs before they’re licensed,” says Schieber, 58, of Paradise, Calif., who was treated at the University of Southern California. “Licensing could take five, maybe 10 years. You could be dead in the meantime.”

Schieber is one of tens of thousands of Americans who have taken part in trials of experimental therapies--treatments for conditions ranging from cancer to migraine headaches that are under study and may, or may not, eventually be approved.

The benefits of participation in drug trials are several: Patients get early access to promising treatments and they get sophisticated care. In addition to any medical improvement, they may derive satisfaction from the sense of contributing to science.

The drawbacks, however, also must be considered. Experimental drugs carry risks, and many turn out not to work. Participants are expected to follow strict rules, limiting such things as other drugs they might take and even whether they may become pregnant.

“They can’t be promised that they will get anything out of it,” says Dr. Lawrence Friedman of the National Heart, Lung and Blood Institute. “Whether they will be put on a treatment that will turn out to be beneficial to them, we can’t promise.”

The following is a guide for patients interested in clinical trials.

What is a clinical trial?

A clinical trial is a research study conducted with patients to assess an experimental treatment for a medical condition. Experimental-drug trials may be conducted only after tests in animals have shown that the drug is not unacceptably toxic.

Trials are funded by the drug’s or device’s sponsor--a pharmaceutical company, research organization or public or private agency. They are usually carried out by researchers working in academic medical centers and other hospitals.

Their purpose is to assess the risks and benefits of the treatment. If the benefits appear to outweigh the risks, the sponsor will file an application with the U.S. Food and Drug Administration asking for approval to market the drug or device.

All new prescription drugs must be proven in clinical trials. Among those now being tested are dozens of possible therapies for such diseases as Alzheimer’s, arthritis, osteoporosis and depression--conditions that especially afflict older Americans. Also,biotechnology products are being tested for everything from stopping the blood clotting that causes heart attacks to speeding up wound healing and to the killing of cancerous cells in those with lung and ovarian cancers.

How do trials work?

Trials are conducted according to a protocol--a plan of action that is drawn up by the researchers and approved by the FDA. The protocol defines which patients will be enrolled, how the treatment will be administered and how its effects will be monitored.

Each protocol contains criteria for selecting participants. For example, some studies will accept only patients who are in a particular stage of a disease. A protocol may specify the age, sex and even sexual orientation of patients to be enrolled. It may exclude patients with certain medical conditions, such as patients with kidney disease or abnormal blood counts. Such restrictions are intended to protect potential subjects from harmful side effects of the drugs.

Drug trials fall into several types:

Phase 1 trials examine the safety of a new drug in a small number of healthy volunteers. The researchers study how the drug is absorbed, metabolized and excreted; they also look for side effects as they steadily increase the dosage.

Phase 2 trials involve patients who have the disease in question. The researchers study whether the drug is effective in treating the patients’ condition and consider any short-term side effects and risks in people who are already ill.

Phase 3 trials expand upon the work done in Phase 2, utilizing hundreds or perhaps thousands of patients. The researchers try to understand better the drug’s risks and benefits and look for the less-common side effects that surface only when large numbers of patients are tested.

In the later phases, trials often compare two groups of patients: One group receives the drug; the other receives an inactive substance, or placebo. By comparing the groups, the researchers hope to learn with more certainty whether the drug really works.

Such studies are often “randomized” and “blinded.” That is, the patients are assigned randomly to one or the other group; and neither the patients nor the researchers should know, until after the results are in, which patients received the drug.

All participants have the right to withdraw from a trial at any time.

How can people get information about what trials are being conducted?

There are few central sources of information for patients or their families seeking information about clinical trials--despite the fact that federal agencies, research groups and drug companies spend more than $1 billion dollars a year testing new drugs.

Patients should first consult their own physicians. Doctors often receive mailings about research projects in their area. They also may know through colleagues or the scientific literature what trials are being done and how to get information.

Newspapers and radio and television stations often report on forthcoming trials or carry public service announcements placed by researchers seeking people to participate in trials. Bulletin boards at large teaching hospitals also may have announcements of upcoming trials.

Academic medical centers, such as those at USC, UCLA, UC Irvine and UC San Diego, are sources of information. Some institutions have patient-referral numbers that people can call for information about ongoing trials.

Officials at UC San Diego refer queries to a “health line,” (619) 543-5820, with operators who have information about ongoing trials. Other institutions suggest that patients telephone the appropriate department--for example, the department of medicine for patients with diabetes.

The National Cancer Institute operates a hot line, (800) 4-CANCER, manned by specialized operators who have access to a computer database called Physician Data Query (PDQ). They can bring to the screen up-to-date information on cancer treatment and trials and mail a printout to the caller.

Patients’ physicians also may contact the National Cancer Institute for information about trials conducted there. The number, for physicians only, is (301) 496-4891. The address is Office of the Director of the Clinical Center, Building 10, Room 2C146, National Institutes of Health, Bethesda, Md. 20892.

For people interested in AIDS drug trials, the National Institute of Allergy and Infectious Diseases has set up a toll-free hot line for information about all NIH-sponsored AIDS studies. The number is (800) TRIALS-A . The lines are open between 6 a.m. and 4 p.m. PST.

Also, numerous newsletters and booklets on AIDS trials are published regularly . The most detailed is the AIDS/ HIV Experimental Treatment Directory published quarterly by the American Foundation for AIDS Research in New York City.

Other sources of information about AIDS drug trials include AIDS Treatment News, published in San Francisco; Gay Men’s Health Crisis in New York City; the San Francisco AIDS Foundation, and the Pharmaceutical Manufacturers’ Assn. in Washington.

What should people consider in discussing participation with their doctors?

Patients should explore fully with their doctors and the researchers every aspect of taking part in a trial. Here are some questions recommended by the National Cancer Institute, the FDA, researchers, ethicists and people who have participated in trials:

What is likely to happen to me with or without this experimental treatment? Patients must understand the alternatives available, researchers say. Some enroll in trials because all other treatments have failed. Others have choices.

Has the drug been tested in humans before? If so, what were the results and side effects? Some experts suggest that patients ask for a copy of the study protocol, read it and ask for clarification of anything that is not clear.

How would participation in the study affect my daily life? Experimental drugs may have unpleasant side effects. Participation in a trial may require frequent visits to a hospital for extensive tests, or even hospitalization.

What will it all cost? Federal rules prohibit sponsors from charging patients for experimental drugs, except under unusual circumstances. However, there could be charges for related patient services and transportation costs.

If I am harmed in the study, who will pay for my medical care? Such expenses may not necessarily be covered. Patients should find out whether their insurance carrier covers costs related to trials and the consequences of taking experimental drugs.

How long will the study last? What kind of long-term follow-up care will be provided? If the drug turns out to work, will I be able to continue to use it? If I am assigned to a “placebo group,” will I be given the drug when the study is over if it proves effective?

“No question is foolish,” the cancer institute advises in a booklet available through its Office of Cancer Communications in Bethesda. “Learn what is available to you. Find out your choices and the risks and benefits of each. Each patient is different.”

What kind of safeguards protect human subjects against exploitation?

Under federal law, all federally funded or federally regulated research studies involving human subjects must be approved by an Institutional Review Board (IRB), a group of overseers appointed by the research institution to screen all research protocols.

The board, composed of scientists and lay people, is expected to make sure that the intended benefits of the research outweigh its expected risks. They must also examine whether the risks have been minimized and the subjects fairly selected.

No study participant may be subjected to unnecessary risk or deprived of needed care simply to find out if a new treatment works. And no patient can be denied therapy, receiving only a placebo, once a drug has been shown to save lives or prevent irreversible damage.

The review board is also expected to make sure that research subjects have given their “informed consent;” that is, that they have agreed to take part only after the researchers have explained orally and in writing the terms and consequences of participation.

Researchers acknowledge, however, that the system is not watertight.

“How many people truly understand what is being communicated to them is a more difficult question,” says Friedman, acting chief of the clinical trials branch at the National Heart, Lung and Blood Institute. “Sometimes people frankly say, ‘Whatever you think is best, I’ll go along with it.’ As much as you tell someone, ‘I want you to understand,’ they may not hear.”

Institutional review boards, clinical trials, laboratories, researchers and drug sponsors all fall under the regulatory jurisdiction of the FDA. The agency attempts to ensure that participants are protected and that the data collected are accurate.

The federal National Institutes of Health also oversees all studies involving NIH funding. In California, state law requires researchers to provide participants with the Experimental Subjects’ Bill of Rights detailing the purpose and process of the trial.

What are the risks for human subjects?

Although most side effects are temporary, the National Cancer Institute points out that some can be permanent and even life-threatening. Some, such as damage to major organs or a second cancer, may not become apparent until after the trial.

Beware of quackery masquerading as legitimate research, the FDA cautions prospective participants. Learn about the researchers and the institution, and insist upon meeting someone in a position of authority.

Do not sign anything that would waive your rights if you are harmed in the study, the FDA warns. People considering enrolling in a study should be suspicious if they are asked to pay for the drug and should ask for proof that the research is FDA-approved.

Are research subjects ever paid for volunteering for trials?

Patients in Phase II and III trials, who may benefit from the treatment being tested, are not usually paid for taking part. However, grants for some Phase I trials may cover payments for the healthy volunteers who agree to participate.

Some experts caution research subjects not to count on any personal gain.

“The motivation to participate in research should always be primarily altruistic, understanding that what you’re trying to do is help people learn and benefit others,” says Arthur Caplan, a medical ethicist at the University of Minnesota.

“If there’s benefit for you, that’s great. But it should not be the overriding motive to get involved. Because more often than not, research does not pan out. And sometimes it causes more harm than good.”